Dear Aventine Readers, 

This week we’re departing from our usual format to share an excerpt of a feature story we are co-publishing with MIT Technology Review about a new frontier in medicine: the human immunome. For years, the galaxy of cells, proteins and molecules that make up our immune systems existed as a mysterious and unknowable force, one with enormous influence over our health but beyond the reach of modern medicine. Thanks to new technologies, that’s now changing, enabling scientists to essentially “read” the immunome for clues about the state of our health. All they need is a blood test. In this story we hear from one of the first people to have his immunome tested, and get a glimpse into a possible future in which such tests are a standard part of primary care, enabling doctors to detect illness before symptoms appear, diseases worsen, or tumors grow and metastasize. We’re including the first section of the story below; if you’d like to read the full version, you can do so here. 

Also in this issue: 

Thanks, as usual, for reading.  And please write with comments, questions and suggestions for future stories by responding to this email or writing to dmattoon@aventineinstitute.org. 

Sincerely, 

Danielle Mattoon
Executive Director, Aventine

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By David Ewing Duncan

It’s not often you get a text about the robustness of your immune system, but that’s what popped up on my phone last spring. Sent by John Tsang, an immunologist at Yale, the text came after his lab had put my blood through a mind-boggling array of new tests. The result — think of it as a full-body, high-resolution CT scan of my immune system — would reveal more about the state of my health than any test I had ever taken. And it could potentially tell me far more than I wanted to know. 

“David,” the text read, “you are the red dot.” 

Tsang was referring to an image he had attached to the text that showed a graph with a scattering of black dots representing other people whose immune systems had been evaluated — and a lone red one. There also was a score: 0.35. 

I had no idea what any of this meant. 

The red dot was the culmination of an immuno-quest I had begun on an autumn afternoon a few months earlier when a postdoc in Tsang’s lab drew several vials of my blood. It was also a significant milestone in a decades-long journey I’ve taken as a journalist covering life science and medicine. Over the years I’ve offered myself up as a human guinea pig for hundreds of tests promising new insights into my health and mortality. In 2001 I was one of the first humans to have my DNA sequenced. Soon after, in the early 2000s, researchers tapped into my proteome — proteins circulating in my blood. Then came assessments of my microbiome, metabolome and much more. I have continued to test-drive the latest protocols and devices, amassing tens of terabytes of data on myself, reporting on the results in dozens of articles and a book called “Experimental Man.” Over time, the tests have gotten better and more informative, but no test I had previously taken promised to deliver results more comprehensive or closer to revealing the truth about my underlying state of health than what John Tsang was offering.

It also was not lost on me that I’m now 20-plus years older than I was when I took those first tests. Back in my 40s I was ridiculously healthy. Since then, I’ve been battered by various pathogens, stresses and injuries, including two bouts of Covid and long Covid — and, well, life.

But I’d kept my apprehensions to myself as Tsang, a slim, perpetually smiling man who directs the Yale Center for Systems and Engineering Immunology, invited me into his office in New Haven to introduce me to something called the human immunome. 

Made up of 1.8 trillion cells and trillions more proteins, metabolites, mRNA and other biomolecules, every person's immunome is different, and is constantly changing. It’s shaped by our DNA, past illnesses, the air we have breathed, the food we have eaten, our age, and the traumas and stresses we have experienced — in short, everything we have ever been exposed to physically and emotionally. Right now, your immune system is hard at work identifying and fending off viruses and rogue cells that threaten to turn cancerous — or maybe already have — and is doing an excellent job of it all, or not, depending on how healthy it happens to be at this particular moment. 

Yet as critical as the immunome is to each of us, this universe of cells and molecules has remained largely beyond the reach of modern medicine — a vast yet inaccessible operating system that powerfully influences everything from our vulnerability to viruses and cancer to how well we age to whether we tolerate certain foods better than others. 

Now, thanks to a slew of new technologies, and to scientists like John Tsang — who is on the steering committee of the Chan Zuckerberg Biohub New York — understanding this vital and mysterious system is within our grasp, paving the way for the creation of powerful new tools and tests to help us better assess, diagnose and treat diseases. 

Already, new research is revealing patterns in the ways our bodies respond to stress and disease. Scientists are creating contrasting portraits of weak and robust immunomes — portraits that someday, it’s hoped, could offer new insights into patient care and perhaps detect illnesses before symptoms appear. There are plans afoot to deploy this knowledge and technology on a global scale, which would enable scientists to observe the effects of climate, geography and countless other factors on the immunome. The results could transform what it means to be healthy and how we identify and treat disease. 

It all begins with a test that can tell you whether your immune system is healthy or not….

The full story continues here. 

Every October, committees in Sweden and Norway name the winners of the Nobel Prizes, celebrating achievements in sciences, literature, economics and peace work. Here, we give you a quick rundown on the winners of the three scientific categories — medicine, physics and chemistry — and explain why they are important.

The Physics prize was awarded to John Clarke, Michel Devoret and John Martinis for contributions to quantum mechanics made decades ago that underpin the development of quantum computing. In the 1980s, the trio studied superconducting circuits known as Josephson junctions — tiny structures in which a layer of insulating material separates two zero-resistance wires. Their work showed that charged particles moving through these circuits behaved as a single quantum system with discrete energy levels, and the system could “tunnel” across the insulating gap. These discoveries revealed how quantum effects could be harnessed and controlled in electrical circuits, an insight that now underpins the design of superconducting qubits, the building blocks of the most advanced quantum computers. Earlier this year, Aventine spoke with Martinis at length about the engineering challenges of turning those ideas into practical machines. “There's a big gap,” he told us, describing the distance between where quantum computing hardware is and where it needs to be, and the profound progress that has been made in the field. In the past, it was never really clear if making that leap was possible. Now, he said, “it's just a matter of closing the gap.”

The Medicine prize was awarded to Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi for discoveries that revealed how the immune system prevents itself from attacking the body — insights now driving new treatments for autoimmune disease. In the 1990s, Sakaguchi identified a previously unknown class of white blood cells, known as regulatory T cells, which act as a brake on the immune system to stop it from overreacting. Less than a decade later, Brunkow and Ramsdell linked a genetic mutation in mice that caused a fatal autoimmune disease, and Sakaguchi showed that the same gene was essential for producing regulatory T cells. Subsequent research revealed that people with conditions such as type 1 diabetes, lupus, rheumatoid arthritis and multiple sclerosis often have too few of these crucial cells. Today, drugmakers are developing therapies designed to boost or mimic regulatory T cells — including personalized cell therapies grown from a patient’s own blood — with the hope of transforming treatment for autoimmune disease.

The Chemistry prize was awarded to Susumu Kitagawa, Richard Robson and Omar Yaghi for creating materials with “super sponge” properties that can trap and store molecules — a breakthrough with potential to curb climate change. In the 1990s, the trio pioneered a class of highly porous materials known as metal-organic frameworks (MOFs). Built by linking metal atoms as nodes with organic molecules into rigid, repeating structures, MOFs have enormous internal cavities and hence huge surface areas — in some cases, the equivalent of a football field packed inside just grams of powder. This structure allows MOFs to soak up carbon dioxide from the air, extract water from humidity and safely store hazardous chemicals. Additionally, some MOFs can also be used to catalyze chemical reactions. More than 100,000 MOFs have now been created, and many researchers see them as key tools for tackling climate change and building a cleaner industrial future.

A new technique turns a woman’s skin cells into eggs. Women who don’t produce eggs — as a result of age, illness or medical treatment — currently have no way to give birth to a genetically related child. Now researchers at Oregon Health & Science University in Portland have shown a possible path forward: turning skin cells into fertilizable human eggs. Writing in Nature Communications, the team collected skin cells from women and transplanted each cell’s nucleus, which contains 46 chromosomes, into donor eggs whose own nuclei had been removed. But here lies a challenge: Eggs contain not 46 but 23 chromosomes, with the other half supplied by sperm during fertilization to form an embryo. To mimic this, the scientists treated the eggs with a compound called roscovitine, which prompted them to eject about half their chromosomes, leaving the remainder to pair with sperm. The wrinkle: This final step in the process produced unreliable results, with no guarantee that exactly 23 chromosomes would be ejected, nor that they would be the right ones. As a result, of the 82 eggs created, fewer than 10 percent developed to the stage at which IVF embryos are typically transferred to the womb because so many embryos had the wrong number or combination of chromosomes. The approach is far from being ready for clinical use, and raises difficult safety and ethical questions. Still, it hints at a future in which women who can’t produce eggs could give birth to genetically related children.

The future of crops could lie in sexless seeds. Many of the world’s highest-yielding crops — corn, rice, tomatoes — are hybrids, created by crossing two varieties to boost yields. The problem: Those benefits are lost after the first crop is harvested, because when hybrids self-pollinate sexual reproduction reshuffles their genes, producing lower-yielding offspring. Researchers are developing a solution, Nature reports, using gene editing to make crops clone themselves. About 300 known species of flowering plants naturally reproduce by cloning, or apomixis, rather than sexual reproduction. Replicating that in staple crops could let farmers replant high-yield seeds year after year, cutting costs and saving seed companies time and labor required to produce hybrids each year. Since the 1990s, scientists have been piecing together how to halt the cell division that creates sex cells and instead triggers simple clonal cell division and parthenogenesis, where embryos grow from unfertilized egg cells. Through gene editing, these steps are now being applied in crops like rice, corn and sorghum. While the potential benefits are significant, crops grown with sexless seeds will face the same regulatory hurdles as other genetically edited crops, and may need to win over skeptical consumers before they can really take root.

AI is helping make research funding decisions. Should it? Sifting through grant applications to decide who gets research funding is complex work that requires deep expertise. Now some awarding bodies are considering whether AI should help make those decisions. Spain's nonprofit la Caixa Foundation is using AI on a trial basis to screen applications, Nature reports, while Imperial College London’s Climate Solutions Catalyst program is using the technology to scan research papers with commercial promise, Science explains. Meanwhile, the US National Institutes of Health banned AI tools from the grant-review process in 2023, and UK Research and Innovation, Britain’s largest funder, prohibited reviewers from using generative AI in 2024. Yet there have been calls to expand the practice: Earlier this year, the Federation of American Scientists urged the US Office of Science and Technology Policy to apply AI analysis to grant applications, arguing that it would “encourage better research investment decisions by both the public and the private sector.” There are obvious reasons for concern: AI could be biased against some avenues of research, make poor choices or leak confidential data. There’s also unease about machines shaping the direction of science. Still, AI might excel at spotting patterns and highlighting promising projects that humans overlook. Most likely, AI will not replace human judgment anytime soon. But it could become embedded in the funding process, quietly influencing which applications make it and which don't.